Mass spectrometers have become common tools in chemical analysis. Generally, mass spectrometers operate by separating ionized atoms or molecules based on differences in their mass-to-charge ratio (m/e). A variety of mass spectrometer devices are commonly in use, including ion traps, quadrupole mass filters, and magnetic sector.
The general stages in performing a mass-spectrometric analysis are:
(1) create gas-phase ions from a sample; (2) separate the ions in space or time based on their mass-to-charge ratio; and (3) measure the quantity of ions of each selected mass-to-charge ratio. Thus, in general, a mass spectrometer system consists of an ion source, a mass-selective analyzer, and an ion detector. In the mass-selective analyzer, magnetic and electric fields may be used, either separately or in combination, to separate the ions based on their mass-to-charge ratio. Hereinafter, the mass-selective analyzer portion of a mass spectrometer system will simply be called a mass spectrometer. Ions introduced into a mass spectrometer are separated in a vacuum environment. Accordingly, it is necessary to prepare the sample undergoing analysis for introduction into this environment. This presents particular problems for high molecular weight compounds or other sample materials which are difficult to volatilize. While liquid chromatography is well suited to separate a liquid sample matrix into its constituent components, it is difficult to introduce the output of a liquid chromatograph (LC) into the vacuum environment of a mass spectrometer. One technique that has been used for this purpose is the electrospray method. The present invention is directed to improvements in the apparatus used to perform the electrospray technique.
The "electrospray" or "electrospray ionization" technique is used to produce gas-phase ions from a liquid sample matrix to permit introduction of the sample into a mass spectrometer. It is thus useful for providing an interface between a liquid chromatograph and a mass spectrometer. In the electrospray method, the liquid sample to be analyzed is pumped through a capillary tube or needle. A potential difference (of for example, three to four thousand volts) is established between the tip of the electrospray needle and an opposing wall, capillary entrance, or similar structure. The needle can be at an elevated potential and the opposing structure can then be grounded; or the needle can be at ground potential and the opposing structure can be at the elevated potential (and of opposite sign to the first case). The stream of liquid issuing from the needle tip is broken up into highly charged droplets by the electric field, forming the electrospray. An inert drying gas, such as dry nitrogen gas (for example) may also be introduced through a surrounding capillary to enhance nebulization (droplet formation) of the fluid stream.
The electrospray droplets consisting of sample compounds in a carrier liquid, are electrically charged by the electrical potential as they exit the capillary needle. The charged droplets are transported in an electric field and injected into the mass spectrometer, which is maintained at a high vacuum. Through the combined effects of a drying gas and vacuum the carrier liquid in the droplets starts to evaporate giving rise to smaller, increasingly unstable droplets from which surface ions are liberated into the vacuum for analysis. The desolvated ions pass through sample cone and skimmer lenses, and after focusing by a RF lens, into the high vacuum region of the mass-spectrometer, where they are separated according to mass and detected by an appropriate detector (e.g., a photo-multiplier tube).
Although the electrospray method is very useful for analyzing high molecular weight dissolved samples, it does have some limitations. For example, commercially available electrospray devices utilizing only electrospray nebulization to form the spray are practically limited to liquid flow rates of 20-30 microliters/min, depending on the solvent composition. Higher liquid flow rates result in unstable and inefficient ionization of the dissolved sample. Since the electrospray needle is typically connected to a liquid chromatograph, this acts as a limitation on the flow from the chromatograph.
One method of improving the performance of electrospray devices at higher liquid flow rates is to utilize a pneumatically assisted electrospray needle. One such device is formed from two concentric, stainless steel capillary tubes. In such a device the sample containing liquid flows through the inner tube and a nebulizing gas flows through the annular space between the two tubes. In one example of such a device, the inner diameter of the inner stainless steel capillary tube is approximately 0.1 mm, and its outer diameter is approximately 0.2 mm. The inner diameter of the outer tube is approximately 0.25 mm, leaving an annular space between the two tubes of thickness 0.025 mm. The inner tube is formed from a conductive material and has a high potential applied across it, to cause the electrospray ionization.
However, the described device has several disadvantages. At high liquid flow rates into this type of electrospray needle, larger size charged and uncharged liquid droplets are formed that can degrade the performance of the mass spectrometer if allowed to enter the spectrometer. In addition, it is difficult to align the two tubes coaxially, so that the tubes are concentric and the annular space between them is uniform. In practice, the inner tube will often contact the wall of the outer tube, as shown in FIGS. 1A and 1B, which are a schematic side view (1A) and end view (1B) showing the relative positions of the inner 50 and outer tubes 52 of a prior art electrospray needle 60. As indicated in the figures, a carrier liquid 54 containing the sample to be analyzed is pumped through inner tube 50, while a nebulizing gas 56 is made to flow through outer tube 52. Due to difficulties in establishing and maintaining the proper alignment between the two tubes, contact between them may occur, as shown in FIG. 1(B). Contact between the tubes results in a lower flow of nebulizing gas in the region of contact. The uneven gas flow will cause uneven gas pressures on the liquid exiting tube 50, and hence a nonuniform pneumatic nebulization of the liquid.
The asymmetry of the nebulizing gas flow arising from non-concentric alignment of the inner and outer tubes causes larger drop sizes, both when using pure pneumatic nebulization, or in combination with the effect of electrospray ionization. The asymmetric gas flow also causes a variation in the optimum location of the electrospray tube assembly with respect to the location of the entrance aperture into the mass spectrometer. This necessitates expensive and time consuming adjustments of the position of the spray assembly because of the variation in the spatial characteristics of the liquid spray.
The relatively high gas flow rates of the prior art device of FIG. 1 that are required to pneumatically assist the nebulization process during electrospray are also undesirable. This is because it is common to utilize an additional heated gas flowing in an opposite direction to the spray to increase the vaporization rate of the droplets and to prevent large droplets from entering the mass spectrometer. A large nebulizing gas flow will, to some extent, counteract the benefit of the drying gas by driving the large droplets into the sampling aperture. The introduction of large droplets into the mass spectrometer increases the noise generated during the mass-analysis.
What is desired is an apparatus which provides a method of producing ions using the electrospray technique which is capable of accommodating increased liquid flow rates. It is also desired that the apparatus provide a uniform flow of nebulizing gas and produce effective nebulization without the use of the high nebulizing gas flow rates found in prior art devices.